An experimental <i>Staphylococcus aureus</i> carriage and decolonization model in rhesus macaques (<i>Macaca mulatta</i>)

Our human model of nasal colonization and eradication of S. aureus is limited by safety issues. As rhesus macaques are closely related to humans and natural hosts for S. aureus, we developed an experimental decolonization and inoculation protocol in these animals. Animals were screened for nasal carriage of S. aureus and 20 carriers were selected. Decolonization was attempted using nasal mupirocin (10 animals) or mupirocin plus trimethoprim/sulfadiazine intramuscularly (10 animals) both once daily for 5 days, and checked by follow-up cultures for 10 weeks. Intranasal inoculation was performed with S. aureus strain 8325–4 in culture-negative animals. 11/20 animals, of which 5 received mupirocin and 6 the combination treatment, became culture-negative for S. aureus for 10 weeks and these 11 animals were subsequently inoculated. Swabs were taken once a week for 5 weeks to test for the presence of the inoculated strain. In 3 animals, strain 8325–4 was cultured from the nose 1 week after inoculation, indicating short-term survival of this strain only, a finding similar to that previously found in our human model. These data demonstrate that rhesus macaques may constitute a relevant animal model to perform S. aureus eradication and inoculation studies with relatively limited invasive handling of the animals.我们现有的金黄色葡萄球菌（Staphylococcus aureus）鼻腔定植与清除人体模型受限于安全性问题。鉴于恒河猴（rhesus macaques）与人类亲缘关系密切，且是金黄色葡萄球菌的天然宿主，我们针对该动物开发了一套实验性去定植与接种方案。首先对实验动物开展金黄色葡萄球菌鼻腔携带状态筛查，最终选取20名阳性携带者。其中10只动物采用鼻腔内莫匹罗星（mupirocin）给药方案，另外10只采用莫匹罗星联合肌肉注射甲氧苄啶/磺胺嘧啶（trimethoprim/sulfadiazine）方案，两种方案均每日给药1次，持续5天；随后通过为期10周的随访培养监测清除效果。待培养结果转阴后，我们对这些动物实施鼻腔接种金黄色葡萄球菌菌株8325–4。20只动物中共有11只在连续10周的培养中均呈金黄色葡萄球菌阴性，其中5只仅接受莫匹罗星治疗、6只接受联合治疗，后续我们对这11只动物进行了接种。随后每周采集鼻腔拭子1次，连续5周，以检测接种菌株的定植情况。其中3只动物在接种后1周即可从鼻腔中分离出菌株8325–4，表明该菌株仅能短期定植，这一结果与我们此前在人体模型中得到的发现一致。本研究数据表明，恒河猴可作为一种合适的动物模型，用于开展侵入性操作相对有限的金黄色葡萄球菌清除与接种相关研究。